{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:53:09Z","timestamp":1782978789527,"version":"3.54.5"},"reference-count":79,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Beta 2 adrenergic receptor (\u03b22 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of \u03b22-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the \u03b22-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8\u2009g\/day with 95% CI -2.4 to -1.085, p\u2009&lt;\u20090.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2\u2009g with 95% CI 1.6 to 10.8, p\u2009=\u20090.013) and non-depleted rats (5.4\u2009g with 95% CI 1.2 to 9.6, p\u2009=\u20090.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p\u2009=\u20090.053) or five weeks in depleted rats (p\u2009=\u20090.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of \u03b22-AR stimulation in this model are largely peripherally mediated. Lastly, we examined \u03b22-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of \u03b22-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of \u03b22-AR agonists to models of surgical injury.<\/jats:p>","DOI":"10.1177\/1744806921997206","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T08:27:18Z","timestamp":1617870438000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Systemic administration of a \u03b22-adrenergic receptor agonist reduces mechanical allodynia and suppresses the immune response to surgery in a rat model of persistent post-incisional hypersensitivity"],"prefix":"10.1177","volume":"17","author":[{"given":"Vipin","family":"Arora","sequence":"first","affiliation":[{"name":"Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo","family":"Morado-Urbina","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young S","family":"Gwak","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee A","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A","family":"Kittel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enriqueta","family":"Munoz-Islas","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Tamaulipas, Reynosa, Tamaulipas, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Miguel Jimenez-Andrade","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Tamaulipas, Reynosa, Tamaulipas, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Alfonso","family":"Romero-Sandoval","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Eisenach","sequence":"additional","affiliation":[{"name":"FM James III Professor of Anesthesiology and Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5268-9506","authenticated-orcid":false,"given":"Christopher M","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, 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